Tomonori Shibata

Modulation of binding properties of amphiphilic DNA containing multiple dodecyl phosphotriester linkages to lipid bilayer membrane

DNA is a promising functional molecule to modify and design lipid membrane functions. In order to use DNA in a hydrophilic-hydrophobic interface including lipid membrane, we have developed an amphiphilic DNA having dodecyl phosphotriester linkages (dod-DNA). Herein, we report the binding of a series of amphiphilic dod-DNAs to the lipid bilayer membrane. Surface plasmon resonance (SPR) assay and fluorescent microscopy showed that dod-DNA having three dodecyl groups at each end strongly bound to lipid membrane due to the slow dissociation rate and the dod-DNA can be used as a linear template for molecular arrangement on the membrane surface.

Fluorescence Probe for Detecting CCG Trinucleotide Repeat DNA Expansion and Slip‐Out

Trinucleotide repeat expansion in genomic DNA causes severe neurodegenerative diseases. Fluorescence probes that bind to trinucleotide repeats have potential as diagnostic tools of trinucleotide repeat disorders. Here, we report a novel tricyclic ligand that binds to CCG trinucleotide repeat DNA. The expansion of the aromatic ring system of the 2‐amino‐1,8‐naphthyridine chromophore from the bicyclic to the tricyclic improved the binding ability to the CCG/CCG motif without losing the selectivity and emissive character. The fluorescence sensitively decreased in response to binding to the CCG trinucleotide repeat. The degree of quenching depended on the number of CCG repeats. In addition, the fluorescence detection was applicable to CCG slip‐out DNA.

1,3-Di(quinolin-2-yl)guanidine binds to GGCCCC hexanucleotide repeat DNA in C9ORF72

Aberrant expansion of GGGGCC (G4C2) hexanucleotide repeat (HNR) in the first intron of C9ORF72 has been found in frontotemporal dementia and amyotrophic lateral sclerosis (FTD/ALD). The non-canonical DNA structures of the expanded repeats are causative to repeat instability leading to contraction and expansion. We demonstrate that 1,3-di(quinolin-2-yl)guanidine (DQG) binds to GGCCCC/GGCCCC (G2C4/G2C4) motif in double stranded DNA and also antisense G2C4 HNR DNA in C9ORF72. Large increase in the melting temperature of dsDNA containing the G2C4/G2C4 motif was confirmed by the binding of DQG. The marked CD spectral changes indicated structural transition of d(G2C4)9 from i-motifs and/or hairpins to DQG-stabilized d(G2C4)9 structures.

DNA cross-link generated by a novel modified DNA containing a formyl group

We here report the synthesis of novel modified nucleic acid containing a formyl group and the evaluation of interstrand cross-linking between the modified DNA and the complementary strand. The synthesis of the formyl-containing oligodeoxynucleotide (ODN) was achieved by a post synthetic modification of corresponding ODN containing a 1,2-diol. The ODN containing the diol moiety was successfully synthesized by a standard phosphoramidite method, and was quantitatively converted to the desired formyl-containing ODN by sodium periodate oxidation. Hybridizaiton of the formyl ODN and the complementary ODN produced the interstrand cross-link between the formyl group and N(6)-exocyclic amino group of adenine.

Fabrication and Evaluation of the Novel Elastomer Based Nanocomposite with Pressure Sensing Function

A novel organic/inorganic composite material which can work as a pressure sensor has been synthesized. This composite basically contains nano-sized carbon particles as conductive filler into an elastomer matrix to achieve pressure sensitive function. The superior pressure sensitive effect was showed at 0.88vol% of carbon particles while in the previous study the micro-sized carbon particle was required above 30vol%. In addition, nano-sized silica particles were added to reinforce electrical insulation properties and to improve the pressure sensing reliability of the composite. The addition of the surface modified silica improved better both the sensing performance and the mechanical strength than the composite containing non-modified silica particles. These polymer-based sensors have economical advantage due to low cost production regardless of the high performance.